The object of this study is the elucidation of the fundamental biochemical mechanisms underlying the process of DNA replication. The proposal is a continuation of present research. By utilizing model systems in vitro, we will define the biochemical functions of proteins, known from genetic analysis to be required for DNA replication. We will identify and characterize proteins, in addition to DNA Polymerase that are essential for propagation of DNA chains. Their biochemical activity will be determined. We will determine the chemical nature of DNA chain initiators and characterize their biosynthesis. A model system will be developed in order to study the biochemistry of replication fork movement. We will then attempt to achieve complete replication of natural DNAs, such that the elements involved in the control (initiative and termination) can be defined. In order to elucidate the mechanism of DNA replication in mammalian cells, similar studies will be conducted in vitro on model systems.